Dendritic cell-derived biomimetic vesicles as cancer vaccine platforms for melanoma immunotherapy

Dendritic cells (DCs) are essential for anti-tumor immunity through recognition of tumor-derived signals and antigens, yet their function is frequently compromised within the tumor microenvironment (TME), enabling immune evasion. Consequently, enhancing DC functionality represents a critical strategy for advancing tumor immunotherapy. The novel engineered biomimetic DC-derived vesicle vaccine, g-diDCVac, integrates the STING agonist diABZI and tumor antigen gp100. Designed for facile modification and enhanced stability, g-diDCVac effectively targets lymph nodes, promotes DC maturation, and elicits potent, antigen-specific T-cell responses. Western blot and ELISA analyses confirm g-diDCVac-driven bone marrow-derived dendritic cell (BMDC) maturation via STING pathway activation. Transcriptomic and proteomic analyses further demonstrate that STING activation triggers downstream cascades, including NF-κB, JAK-STAT, and antigen processing and presentation pathways. Significantly, in therapeutic and prophylactic melanoma models, g-diDCVac stimulates robust in vivo immune responses, remodels the immunosuppressive TME, markedly suppresses tumor progression, and extends survival. These findings establish the therapeutic potential of this DC vesicle vaccine and support DC extracellular vesicle-based nanovaccines for cancer immunotherapy, providing compelling rationale for developing enhanced cancer vaccines.